The Alzheimer Pandemic: Is Paracetamol to Blame? (2013)

I am a programming neuroscientist who studies Alzheimer's, and I would like to say that, while it is not entirely clear whether or not N-acetylcysteine will prove fruitful as a therapeutic for Alzheimer's, PA/tylenol is not the same thing as N-acetylcysteine, so the NSAID link is irrelevant in that regards. The link between these two is that N-acetylcysteine is used as a treatment for overdose of PA - because of a metabolite which is produced following high consumption of PA (NAPQI). Importantly, this link does not indicate that they have inversely correlated mechanisms of action under normal circumstances. PA may not be worth exploring further, but the understanding of N-acetylcysteine is still worth exploring. Note I do not study this myself, just putting in my two cents.

This is from 2013. Why has it seen essentially no news coverage? I can't, for instance, easily find it on sites like Science Based Medicine; you'd think they'd have lit up over this.

I read on Paracetamol's wikipedia page that "Paracetamol also modulates the endogenous cannabinoid system" (https://en.wikipedia.org/wiki/Paracetamol#Society_and_cultur...). Given recent studies that indicate Alzheimer's can be treated by THC (http://www.ncbi.nlm.nih.gov/pubmed/25024327), it seems that there's some kind of connection between Alzheimer's and the endogenous cannabinoid system. If that's true, then it could mean paracetamol is not really the "cause" of Alzheimer's, but rather a part of the real cause: disruption or malfunction of our brain's cannabinoid receptors. Perhaps we will finally be able to prove, scientifically and neurologically, that these receptors cannot be ignored, they play a crucial role in our survival.

Just so people are clear, paracetamol is Tylenol.

Is it just me, or is the "ANALGESICS AS RISK FACTORS FOR F-AD: (2) EPIDEMIOLOGY" section really uncompelling and the epidemiological evidence seems to amount to a few inconsistent cross-sectional studies with no particularly large correlations like implied, and a note that both paracetamol and Alzheimer's have increased over the past two centuries or so?

dear correspondents, thank you all for your various comments. much as i would like to engage with you all i fear i cannot. i am in poor health and have short life expectation. i would like to make some general comments. first, science is a serious professional activity, too important to be discussed in a trivial or superficial manner. if you want to join the debate, please read both my papers of 2014. a search engine should find them with jones alzheimer's 2014 allergy. i cannot help it if you find them too hard to follow. i see it as my job to provide new conclusions from known facts and not to give seminars. second, open access cost me good money, in excess of £1000; quite a sum for a pensioner. third, i cannot deal with the many misunderstandings of my work. i never suggested that acetyl cystein is an antidote for Alzheimer [ad]. neither do i accept the findings of stewart et al [1997], whose paper i criticised with good reason in the first of my 2014 papers. fourth, paracetamol is a wholly UNTESTED drug, and for that reason needs special attention. there have been a number of reports of the harm it does to the unborn child. i would like to provide references but my home was raided while i was in hospital in the summer and ALL my notes were stolen. i have never come across a similar incident, which gives some idea of the trenchant opposition to my work. fifth, someone aks why there has been no news coverage? because i am totally isolated here. my emails are read, my mail is often impounded, the telephone is tapped and at least one room is bugged. this is a big operation thought to be on behalf of a huge drug company to keep the whole thing under wraps. thank you for your interest, compliments of the season, sincerely, robert jones.........

Published in 2013.

My comments on this made last year:

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Once you know enough of the basics in a field to get by as a layperson, you'll find that scientific literature is far removed from being dry and uncontroversial. There are always heretics and novel positions being advanced - most of them wrong, but all new fields and new directions start with a few heretics, and the mainstream is consistently overturned with time, to be replaced with the new consensus. Distinguishing a good speculative hypothesis from a work of overreaching fancy can be a challenge wherever you stand in the hierarchy of knowledge, and the good-looking fallacies far outnumber the seeds of tomorrow's scientific mainstream. This is why few researchers bother to spend any time on reviewing this sort of thing when there are so very many other demands on their time.

One of the SENS Research Foundation folk turned up the open access paper on paracetamol and Alzheimer's in the course of ongoing reviews of scientific literature relevant to aging, and thought it heretical enough to share as an item of interest - as a curio well outside the current consensus, not as anything to be acted on. It makes for a good read, and is well-researched, but I think that ultimately the points being made here can be explained away by the coincidence of development of medical technology, increasing longevity, and increasing wealth. When it comes down to the biochemistry, the dots aren't really joined well enough to be very compelling.

So I offer this as an example of the fact that if you go digging around, you'll find very interesting papers that are well-researched, highly speculative, and probably wrong. The author of this paper has been advancing his theory for more than a decade, evidently without gathering much support. That is all part and parcel of the scientific process.

The conclusion of the paper, that Alzheimer's is an artifact of paracetamol use, is something of a bold conclusion, and as I noted above I don't think it stands too well against Occam's razor. It is simpler to point to rising wealth driving the sedentary, high-calorie lifestyle that greatly raises the risk of suffering age-related diseases such as Alzheimer's, and note that this coincides with advances in medical technology that allow for more reliable identification of the condition, progress in other technologies that improve record-keeping and reliability in medicine, and the concurrent trend in rising life spans such that more people survive to ages in which neurodegenerative conditions become a significant risk.

I still suggest you read the paper, as you'll find that a great deal of interesting historical data is referenced therein. You'll probably learn some things that you didn't know about the history of painkillers, for example.

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TLDR: Disease Foo has become more common in the past few hundred years. You know what else has become more common in the past few hundred years? Bar! Therefore, Bar causes Foo, QED.

Betteridge's law